The essence of this proposal is to capitalize upon current and future inflow of chromosome studies of children and their families to ask potentially answerable questions regarding chromosome structure, function and behavior. The questions particularly concern minor and major chromosome rearrangements and aneuploidy, as well as normal apparently non-variant chromosomes. Cell types to be studied include lymphocytes, lymphobalsts, fibrobalsts, neurons and meiotic cells in various stages of the cycle including interphase, prophase and metaphase. Techniques to be used include chromosome banding, light and fluorescent microscopy, autoradiography, photometry, densitometry and cell hybridization. We know little but intend to learn more about the structure, function and linkage relations of minor chromosome variants. They should prove suitable anchors for gene mapping via somatic cell hybridization. We likewise do not know much but want to learn more about the formation, structure and behavior of major chromosome rearrangements. These include Robertsonian, reciprocal and insertional translocations and inversions. Their use in gene mapping has been sparse; we intend to employ them whenever possible for this purpose. We will continue to explore the location, behavior and function of marked chromosome segments in interphase and of whole chromosomes in prophase. We will also pursue autosomal aneuploidy to learn whether there is a generalized loss of control over somatic chromosome distribution. Chromosome breakage in several genetic diseases (ataxia-telangiectasia, Fanconi's and Bloom's syndromes) will be studied to learn if the breaks are randomly distributed and whether (with hybridization) the responsible genes can be mapped. This proposal is a coordinate one with those being submitted by R. Ellen Magenis and Everett W. Lovrien, with whom we share space, facilities and collaborate closely. The overall aim of this proposal and of the two coordinate proposals by Drs. Magenis and Lovrien is to establish Oregon firmly as a major center for the study of human chromosome structure, function and behavior.